The invention is directed to overcoming the problem associated with obtaining well-dispersed colloidal particles of uniform size and shape of ferrites containing manganese(II), zinc(II), mixed manganese(II)-zinc(II), iron (II), barium(II), cobalt(II), and nickel(II). Colloidal particles of manganese(II) and zinc(II) or mixed manganese(II)-zinc(II) ferrites of uniform shape and size have not previously been reported. The invention provides a method of preparation of magnetic metal oxide particles in the presence of a polymer, solubilized in an aqueous medium wherein the colloidal particles of ferrites containing manganese(II), zinc(II), mixed manganese(II) -zinc(II), iron(II), barium(II), cobalt(II), and nickel(II), are of a well-defined and uniform shape and size and are dispersed as single particles in an aqueous media.
Ferrites containing manganese and/or zinc in fine particle form represent an important class of ferromagnetic materials. Most preparations of manganese ferrites have been carried out at high temperatures (1000.degree.-2000.degree. C.) from solid solutions to produce large crystallites [German Patent, DE 3619746 Al, Japanese Patents, JP 8791423 A2 and JP8791424 A2]. Lower temperature (350.degree. C.) decomposition of a mixed Mn-Fe oxalate, followed by reduction with H.sub.2 /H.sub.2 O, gave a polycrystalline powder which was characterized as a solid solution of Fe.sub.3 O.sub.4 and MnFe.sub.2 O.sub.4. Low temperature methods assure crystallization of manganese ferrite in the spinel structure as ferrimagnetic fine particles [R. Bendaoud et.al., IEEE Trans. Magnetics, MAG-23: 3869-3873 (1987)].
Notable progress in obtaining monodispersed magnetite and ferrite (Co.sup.2+, Ni.sup.2+) particles has been made [T. Sugimoto and E. Matijevic, J. Coll. Interface Sci., 74: 227-243 (1980); H. Tamura and E. MatiJevic, J. Coll. Interface Sci., 90: 100-109 (1982); A. E. Regazzoni and E. Matijevic, Corrosion, 38: 212-218 (1982); A. E. Regazzoni and E. Matijevic, Colloids Surf., 6: 189-201 (1983); E. Matijevic, J. Coll. Interface Sci., 117: 593-595 (1987); X. J. Fan and E. Matijevic, Patent Application WO 88/05337]. In every case, however, the bulk of the magnetic particles in suspension is irreversibly aggregated into large clusters that have a wide range of sizes and shapes. Also, the hydrophobic surface of bare metal oxide particles not only contributes to their agglomeration but also makes them unsuitable for manipulation in aqueous solutions of biological molecules, buffered near pH 7.
Some success in the preparation of polymer-magnetite composite particles of uniform spherical shape has been achieved through the emulsion polymerization of vinyl aromatic monomer in the presence of ferrofluid seed particles which become embedded inside the polymer latex [U.S. Pat. No. 4,358,388 and 4,783,336]. Control over the size of the magnetic latex particles is poor, therefore, resulting in particles with a wide range of sizes and magnetic content. When external surface carboxylic acid groups are introduced, the magnetic latex particles are hydrophilic to some degree but still cannot be dispersed as single particles in buffered aqueous media near pH 7. Coating of these particles by covalent attachment of aminodextran has been carried out to give the particles a hydrophilic shell. These aminodextran-coated particles are stable in an aqueous buffer and have been covalently linked with various monoclonal antibodies (IgG and IgM) for cell depletion.
Uniform polymer-ferrite or -maghemite (magnetic hemalite) composite particles have been prepared by crystallizing the magnetic oxide inside uniform spherical and porous polymer particles [International Patent Appliction WO83/03920; J Ughelstad et.al. in "Microspheres: Medical and Biological Applications", Eds., A. Rembaum and Z. A . Tokes, CRC Press, Inc., Boca Raton, FL, 1988]. Metal salts were diffused into the pores of the particle and adjustment of pH or oxidation was carried out as required. Alternatively, magnetic porous particles of metal oxide were first prepared and then, the pores were filled and covered with hydrophobic polymer. In both cases it was recognized that an additional hydrophilic polymer coating was required for better specific bead performance.
Solubilized polymers have been used to control the nucleation and growth of various metal particles. The concept of nucleation of metal particles in the domain of the polymer molecule was first described in the formation of cobalt organosols by thermal decomposition of dicobalt octacarbonyl in toluene and other organic solvents with various solubilized polymers [P. H. Hess and P. H. Parker, (Jr., J. Appl. Polym. Sci, 10: 1915-1927 (1966)]. The classic protective agent for colloids is gelatin ["The Theory of the Photographic Process", T. H. James, MacMillan Publ. of polyacrylic acid and polyethyleneimine-N-alkylacetic acid have been used to obtain stable hydrosols of gold, silver, copper, and platinum metals [H. Thiele and H. S. von Levern, J. Coll. Sci., 20: 679-694 (1965)]. Colloida dispersions of very small rhodium, iridium, osmium, palladium, platinum, silver, and gold particles in ethanol or methanol with polyvinyl alcohol (PVA) or polyvinylpyrrolidone (PVP) as stabilizer have been prepared [H. Hirai, J. Macromol. Sci. Chem., A12: 1117-1141 (1978); O. Siiman et.al., Chem. Phys. Lett., 100: 163-168 (1983); A. Lepp and O. Siiman, J. Coll. Interface Sci., 105: 325-341 (1985); O. Siiman and W. P. Hsu, J. Chem. Soc., Faraday Trans. 1, 82: 851-867 (1986)] . Functional, soluble polymers have been used to control the formation of colloidal dispersions of selenium and iron [T. W. Smith and R. A. Cheatham, Macromolecules, 13: 1203-1207 (1980); T. W. Smith and D. Wychick, J. Phys. Chem., 84: 1621-1629 (1980)].
Recently, hydroxypropyl cellulose was used in the formation and stabilization of monodisperse TiO.sub.2 particles by hydrolysis of titanium tetraethoxide in ethanol [J. H. Jean and T. A. Ring, Colloids Surf., 29:273-291(1988)].
Monodispersed metal ferrite particles have several important applications. They have magnetic properties that are useful for the manufacture of transformers, inductors, audio and video recording heads. Gelatin-coated MnFe.sub.2 O.sub.4 or ZnFe.sub.2 O.sub.4 particles with attached monoclonal antibody represents a completely biodegradable magnetic separation system for biological cells. The particles, coating, and any attached monoclonal antibody can be phagocytosed without killing the cells. Also, gelatin, monoclonal antibody, and cell(s) may be separated from the magnetic particles by enzymatic cleavage of peptide bonds in gelatin, such as, by using trypsin, papain, collagenase and other digestive enzymes. The particles may, furthermore, be used as specific cell surface markers. This invention provides for effective preparation of such monodispersed metal ferrite particles.